The disease stole his right eye and most of his left and destroyed his kidneys, but now, more than four decades after his diabetes diagnosis, Gary Kleiman is free.

With transplanted insulin-producing cells regulating the amount of glucose in his body, Kleiman, 50, is done with the insulin pump, with the constant monitoring of food and drink, with the frightening spikes and dangerous drops of his blood sugar.

'For the first time in a long, long time, I can think about a future,' said Kleiman, executive director for medical development at the University of Miami's Diabetes Research Institute, where he received the experimental islet cell transplant a year ago.

For now, Kleiman and fellow islet cell recipients still require powerful immunosuppressants to keep their bodies from rejecting the tiny cell clusters, called islets, purified from a donor's pancreas. And doctors don't know how the islets will work long-term. Insulin-free for three years come June, Rachel Harris, 34, is believed to be the world's longest insulin-free diabetic.

Harris flew from Atlanta to join her UM doctors, and other researchers from across the nation, at A World of Hope Conference, 'From Research to Reality: Islets, Stem Cells, and Other Therapies,' in Bal Harbour last weekend to discuss the ongoing work toward a cure.

'There has been more progress in the last four years than the preceding two decades,' said Dr. Camillo Ricordi, scientific director of the DRI. ``But it's not a final victory.'

In diabetes, which strikes an estimated 16 million Americans, the pancreas loses the ability to produce or process insulin. With blood sugar uncontrolled, the disease can ultimately lead to stroke, heart disease, gangrene, blindness and kidney failure.

Rather than try to transplant the entire pancreas -- major surgery with a complicated recovery -- Ricordi pioneered a method to isolate cells in the pancreas that produce insulin. In a four-to-six hour process, the pancreas is broken down by enzymes, islet cells purified. They are then injected through a vein into the recipient's liver, where they perform the delicate task of keeping blood sugar balanced.

Kleiman keeps a photograph of the surgery on his computer, along with a close-up of the islets. He's smiling in the photo, but said that as he stayed awake during the transplant, he could only think of his friends with diabetes who had died along the way, before transplantation became a possibility.

Still, even with a new regimen of anti-rejection drugs, the transplant is experimental, Ricordi said, not recommended for those with diabetes under control. Kleiman was on anti-rejection drugs anyway, following two kidney transplants, but these drugs bring with them a host of side-effects -- tremors, for instance, insomnia, nausea, dangerous infection.

'Our major problem right now is that we have to give powerful generalized immunosuppression,' said Dr. Luca Inverardi, co-director of the cell transplant center at DRI. ``What is the solution? If you could reeducate the immune system not to reject the transplanted organ, without compromising its ability to defend itself.'

Bone marrow transplants are one possibility, researchers said.

If transplanted bone marrow 'coexists' with existing bone marrow, the recipient would effectively have two different immune systems, both working together. This way, the body would accept any transplanted tissue or organs from the bone marrow donor.

The principle has been shown to work for cancer patients who undergo a bone marrow transplant, Inverardi said. But it's not yet a safe protocol to try for individuals who don't otherwise need the marrow transplant.

Even if researchers do find a way to make the body accept the transplant without anti-rejection drugs, they'll be faced with a need far outranking the donor supply. So they are working, first, to maximize the yield from each available pancreas.

Currently, some patients require infusions from one pancreas, others from two or even three. Inverardi said they hope to bring that number down to one-half pancreas per patient, but they'll still need alternative sources.
One hope are 'precursor cells.' These are cells in the pancreas that can become insulin-producing islets if a person gains a large amount of weight or becomes pregnant.

The task is to find out what triggers these cells to become islets, and harness that knowledge to produce islets in the lab, Inverardi said.

Researchers are also looking to transfuse islets from other species, like pigs. Of course, Inverardi said, injecting pig insulin would trigger an even more severe rejection than human insulin.

And while they are excited, the diabetes researchers are hesitant to commit to any timeline as to when the worldwide research could translate into a coveted diabetes cure.

Kleiman's niece was recently diagnosed with diabetes, exactly 43 years after Kleiman's own diagnosis. Kleiman was shocked, but said his story gives her, and the millions of other insulin-dependent diabetics, reason to hope.

'I think people could use us as a barometer of what's happening to see this is working,' he said.

Copyright 2004 The Miami Herald